摘要
目的探讨金帕龙对阿尔茨海默病(AD)模型大鼠记忆功能障碍的改善作用及可能的机制。方法健康雄性SD大鼠20只按随机数字表法分成对照组、模型组、低剂量组和高剂量组,每组5只。对照组不进行任何处理,后3组无菌条件下在海马CA3区注入2μL0.5μmol/L渥曼青霉素;高、低剂量组24h后进一步在海马CA3区注射5μL 1mmol/L、5μL 0.5mmol/L金帕龙。3周后使用水迷宫实验测定各组大鼠的记忆功能。随后取海马CA3区标本,应用免疫组化染色检测各组标本的细胞周期蛋白依赖性激酶-5(CDK5)、糖原合成酶激酶-3β(GSK3β)以及磷酸化tau蛋白(p-tau)表达;采用Western blotting实验检测突触蛋白Ⅰ表达。结果(1)水迷宫实验:与模型组大鼠比较,高、低剂量组大鼠潜伏期显著缩短,差异有统计学意义(P<0.05)。与模型组和低剂量组大鼠比较,高剂量组大鼠穿越平台次数明显增多,滞留时间明显延长,差异有统计学意义(P<0.05)。(2)免疫组化染色实验:与模型组比较,高剂量组大鼠CDK5表达量、GSK-3β表达量和p-tau表达量均明显降低,差异有统计学意义(P<0.05)。(3)Western blotting实验:与模型组比较,高剂量组大鼠突触蛋白Ⅰ表达量明显增加,差异有统计学意义(P<0.05)。结论金帕龙可通过降低AD大鼠海马部位CDK5、GSK-3β及p-tau蛋白表达,增强突触蛋白Ⅰ表达,改善AD大鼠的记忆功能。
Objective To investigate the effect of Kenpaullone on memory dysfunction in Alzheimer's disease(AD)model rats and its possible mechanism.Methods Twenty healthy male SD rats were divided into control group,model group,low dose group and high-dose group by random number table method(n=5).The rats in the control group did not receive any treatment;2μL 0.5 mol/L wortmannin was injected into the hippocampal area of rats in the later three groups via stereotaxic method;The rats in the high-dose and low-dose groups were further injected with 5μL 1 mmol/L and 5μL 0.5 mmol/L Kenpaullone 24 h after wortmannin injection.Three weeks after Kenpaullone injection,the memory functions of rats in each group were measured by water maze.The expressions of cyclin-dependent kinase-5(CDK5)/p25,glycogen synthase kinase-3β(GSK3β)and phosphorylated tau(p-tau)in the hippocampal CA3 regions were determined by immunohistochemistry.Synapsin I expression was detected by Western blotting.Results(1)In the water maze experiment:as compared with those in the model group,the incubation periods of rats in the high-dose and low-dose groups were significantly shortened(P<0.05);as compared with those in the model group and the low-dose group,the times of crossing the platform and the retention time in the high-dose group were significantly increased(P<0.05).(2)In immunohistochemical staining,as compared with the model group,the high-dose group had significantly decreased CDK5,GSK-3β,and p-tau expressions(P<0.05).(3)Western blotting indicated that as compared with that in the model group,synapasin I expression was significantly increased in the high-dose group(P<0.05).Conclusion Kenpaullone can decrease the GSK-3β,CDK5/p25 and p-tau protein expressions and increase synapsin I protein expression in the hippocampus CA3 region,and improve cognitive dysfunction of the rats.
作者
李汉文
武衡
Li Hanwen;Wu Heng(Department of Internal Medicine,Hunan University of Medicine,Huaihua 418000,China;Department of Neurology,First Affiliated Hospital of Nanhua University,Hengyang 421000,China)
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2019年第4期331-336,共6页
Chinese Journal of Neuromedicine
